9-Deoxy-9-methylene-inter-oxa-13,14-didehydro-16-phenyl-17,18,19,20-tetranor-PGF1 compounds

ABSTRACT

The present invention relates to novel 9-deoxy-9-methylene-interoxa-13,14-didehydro-16-phenyl-17,18,19,20-tetranor-PGF 1  compounds. These compounds are useful pharmacological agents, and are useful for the same purposes as the corresponding PGE-type compounds.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of Ser. No. 786,249, filed Apr. 11, 1977, now issued as U.S. Pat. No. 4,118,584.

The present invention relates to novel 9-deoxy-9-methyleneinter-oxa-13,14-didehydro-16-phenyl-17,18,19,20-tetranor-PGF₁ compounds, the essential material constituting a disclosure of which is incorporated here by reference from U.S. Pat. No. 4,118,584. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein M₁ is ##STR2## wherein R₅ is hydrogen or methyl;wherein L₁ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; wherein Z₈ is --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ -- wherein g is one, 2, or 3; wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl; wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alky of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation, and the 1,11- or 1,15-lactones thereof.
 2. A prostaglandin analog according to claim 1, wherein M₁ is ##STR5##
 3. A prostaglandin analog according to claim 2, wherein g is
 3. 4. 9-Deoxy-9-methylene-2a,2b-dihomo-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 3. 5. 9-Deoxy-9-methylene-2a,2b-dihomo-15-epi-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 3. 6. A prostaglandin analog according to claim 2, wherein g is
 1. 7. A prostaglandin analog according to claim 6, wherein at least one of R₃ and R₄ is methyl.
 8. 9-Deoxy-9-methylene-15-epi-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 7. 9. A prostaglandin analog according to claim 6, wherein at least one of R₃ and R₄ is fluoro.
 10. 9-Deoxy-9-methylene-15-epi-16,16-difluoro-16-phenyl-17,18,19-20-tetranor-13,14-didehydro-5-oxa-PGF.sub.1, a prostaglandin analog according to claim
 9. 11. A prostaglandin analog according to claim 6, wherein R₃ and R₄ are both hydrogen.
 12. 9-Deoxy-9-methylene-15-epi-16-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF.sub.1, a prostaglandin analog according to claim
 11. 13. A prostaglandin analog to claim 1, wherein M₁ is ##STR6##
 14. A prostaglandin analog according to claim 13, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 15. A prostaglandin analog according to claim 14, wherein g is
 3. 16. A prostaglandin analog according to claim 15, wherein at least one of R₃ and R₄ is methyl.
 17. 9-Deoxy-9-methylene-2a,2b-dihomo-16-methyl-16-phenyl-18,19,-20-trinor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 16. 18. A prostaglandin analog according to claim 15, wherein at least one of R₃ and R₄ is fluoro.
 19. 9-Deoxy-9-methylene-2a,2b-dihomo-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 18. 20. A prostaglandin analog according to claim 15, wherein R₃ and R₄ are both hydrogen.
 21. 9-Deoxy-9-methylene-2a,2b-dihomo-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 20. 22. A prostaglandin analog according to claim 14, wherein g is
 1. 23. A prostaglandin analog according to claim 22, wherein at least one of R₃ and R₄ is methyl.
 24. A prostaglandin analog according to claim 23, wherein R₃ and R₄ are both methyl.
 25. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-5-oxa-PGF₁, tris-(hydroxymethyl)aminomethane salt, a prostaglandin analog according to claim
 24. 26. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-5-oxa-PGF₁, methyl ester, a prostaglandin analog according to claim
 24. 27. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 24. 28. A prostaglandin analog according to claim 22, wherein at least one of R₃ and R₄ is fluoro.
 29. A prostaglandin analog according to claim 28, wherein R₃ and R₄ are both fluoro.
 30. A prostaglandin analog according to claim 29, wherein R₅ is methyl.
 31. 9-Deoxy-9-methylene-15-methyl-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 28. 32. A prostaglandin analog according to claim 29, wherein R₅ is hydrogen.
 33. 9-Deoxy-9-methylene-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 32. 34. A prostaglandin analog according to claim 22, wherein R₃ and R₄ are both hydrogen.
 35. A prostaglandin analog according to claim 34, wherein R₅ is methyl.
 36. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, tris-(hydroxymethyl)aminomethane salt, a prostaglandin analog according to claim
 35. 37. 9-Deoxy-9-methylene-15-methyl16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, methyl ester, a prostaglandin analog according to claim
 35. 38. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 35. 39. A prostaglandin analog according to claim 34, wherein R₅ is hydrogen.
 40. 9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF.sub.1, methyl ester, a prostaglandin analog according to claim
 39. 41. 9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-5-oxa-PGF₁, a prostaglandin analog according to claim
 39. 